CCR10+ ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma

被引：25

作者：

Beuraud, Chloe ^{[1
]}

Lombardi, Vincent ^{[1
]}

Luce, Sonia ^{[1
]}

Horiot, Stephane ^{[1
]}

Naline, Emmanuel ^{[2
]}

Neukirch, Catherine ^{[3
]}

Airouche, Sabi ^{[1
]}

Perchet, Thibaut ^{[4
]}

Golub, Rachel ^{[4
]}

Devillier, Philippe ^{[2
]}

Chollet-Martin, Sylvie ^{[5
]}

Baron-Bodo, Veronique ^{[1
]}

Nony, Emmanuel ^{[1
]}

Aubier, Michel ^{[3
]}

Mascarell, Laurent ^{[1
]}

Moingeon, Philippe ^{[1
,6
]}

机构：

[1] Stallergenes Greer, Res Dept, Antony, France

[2] Univ Paris Saclay, Foch Hosp, Airway Dis Dept, UPRES EA 220, Suresnes, France

[3] Paris Diderot Univ, Bichat Hosp, Dept Pulm Med, Fac Med,INSERM,UMR1152, Paris, France

[4] Inst Pasteur, Unit Lymphopoiesis, Dept Immunol, INSERM,U1223, Paris, France

[5] Paris Sud Univ, INSERM, UMRS996, Chatenay Malabry, France

[6] Servier, Res & Dev, Suresnes, France

来源：

ALLERGY | 2019年 / 74卷 / 05期

关键词：

INNATE LYMPHOID-CELLS; AIRWAY INFLAMMATION; ATOPIC-DERMATITIS; TYPE-2; IMMUNITY; CHEMOKINES; EXPRESSION; PSORIASIS; DISEASE; CCL27;

D O I：

10.1111/all.13679

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

BackgroundWe previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10. MethodHerein, CCR10(+) ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10(+) and CCR10(-) ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR. The role of CCR10(+) ILC2s in asthma pathophysiology was studied in allergen-treated mice. ResultsWhen compared to healthy controls, CCR10(+) ILC2s are enriched in the blood of both allergic and non-allergic severe asthmatic patients, and these cells are recruited to the lungs. Plasma concentrations of the CCR10 ligand CCL27 are significantly increased in severe asthmatics when compared to non-asthmatic patients. CCR10(+) ILC2s secrete little T(H)2 cytokines, but exhibit ILC1-like properties, including a capacity to produce IFN-. Also, single-cell analysis reveals that the CCR10(+) ILC2 subset is enriched in cells expressing amphiregulin. CCR10(+) ILC2 depletion, as well as blocking of IFN- activity, exacerbates airway hyperreactivity in allergen-challenged mice, providing evidence for a protective role of these cells in allergic inflammation. ConclusionsFrequencies of circulating CCR10(+) ILC2s and CCL27 plasma concentrations represent candidate markers of asthma severity. The characterization of CCR10(+) ILC2s in human samples and in mouse asthma models suggests that these cells downregulate allergic inflammation through IFN- production.

引用

页码：933 / 943

页数：11

共 47 条

[1] IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs [J].